Breast cancer is the most commonly diagnosed cancer in women after non-melanoma skin cancer, and is the second leading cause of cancer deaths after lung cancer. Clinical evaluations have established that mammography screening with or without clinical breast examination, may decrease breast cancer mortality. Therefore, mammography remains the gold reference standard today for breast cancer screening, however, it suffers from a variety of limitations such as radiation hazard, considerable patient discomfort, higher false readouts with denser breast tissue, sensitivity & specificity varies according to technician's skill (60-80%), and typically over-diagnoses. Currently used serum/blood biomarkers (e.g. CA27.29, CA15.3, CEA, HER-2) are mainly used in monitoring and surveillance due to poor sensitivity and specificity for other than those applications. Patient management following initial suspicion of breast cancer usually includes confirmation of the diagnosis, evaluation of stage of disease, surgical removal of the tumour tissue and selection of a therapy. The survival rate to breast cancer is over 90% when detected and treated early with existing therapies.
Ovarian cancer is the second most common gynaecological cancer and is the ninth most common cancer but is the fifth most deadly. In the USA, ovarian cancer occurs in 1 of 2′500 post-menopausal women and is the most lethal gynaecological malignancy, accounting for 5-6% of all cancer-related deaths (Kulasingam et al., 2010, Nature Reviews, Cancer, 10, 371-377). The main problem is that ovarian cancer does not usually lead to alarming symptoms. A large majority of patients have advanced cancer and widespread disease at presentation. This late detection of ovarian cancer explains why the overall survival rate for ovarian cancer is less than 40%, whereas that the survival rate is close to 90% when diagnosed at early stage. Furthermore, there is no effective screening test that can detect the disease in its early stages. For women at increased risk, prophylactic oophorectomy is usually considered after the age of 35 if childbearing is complete. Patients with clear cell histology appear to have a worse prognosis.
The most studied/used marker for ovarian cancer is CA125 which is a protein antigen found at abnormally high levels in the blood of many ovarian cancer patients, but was also found to be elevated in non-cancer cases (e.g. pregnant women). Furthermore, the CA125 biomarker was found to have a low sensitivity and specificity and is essentially used for monitoring response to treatment for ovarian cancer. Although CA125, has no prognostic significance when measured at the time of diagnosis, it seems to show a correlation with survival with the progression of the disease, especially when measured after the course of chemotherapy for patients with stage III or stage IV disease. Another method used for early detection of ovarian cancer is trans-vaginal ultrasound. However, this method is known to have a very low positive predictive value of about 3% according to a major recent study (Menon et al. 2009, Lancet Oncol., 10, 327-40).
In most families affected with the breast and ovarian cancer syndrome or site-specific ovarian cancer, genetic linkage has been found to the BRCA1 locus on chromosome 17q21 (Easton et al., 1993, Am. J. Hum. Genet., 52 (4): 678-701). BRCA2, responsible for some forms of inherited ovarian and breast cancer, has been mapped by genetic linkage to chromosome 13q12 (Wooster et al., 1994, Science 265 (5181): 2088-90, 1994). The majority of those women with those mutations presumably have family members with a history of ovarian and/or breast cancer; therefore, they may have be more vigilant and inclined to participate in cancer screening programs that may have led to earlier detection. However, for other women populations, early detection remains more uncertain.
Several tests using biomarkers in blood have attempted to make the diagnosis of ovarian (OC) and breast cancer (BC) less invasive, more accurate, less invasive or less risky than the use of known diagnostic tools, i.e. mammography for BC. However most of them have been discarded after a series of unfortunate misinterpretations or due to insufficient experimental evidence (Kulasingam et al., 2010, above).
Therefore, there is an emerging need for developing new methods and tools for providing an easy, reliable (minimum sensitivity and specificity), non-invasive and early diagnosis of breast and/or ovarian cancers, before those cancer cause symptoms.